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Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.
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COVID-19 , Neoplasias , Humanos , Pandemias , COVID-19/epidemiologia , Pesquisa sobre Serviços de Saúde , Europa (Continente)/epidemiologia , Europa Oriental , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapiaRESUMO
AIM: In January 2017, a new funding model for diagnostic genetic testing in cancer was introduced in Poland. OBJECTIVES: The aim of this study was to assess the impact of changing the funding model for genetic diagnosis in oncology on improving access to personalized medicine in Poland between 2017 and 2019. METHODS: The analysis included data on settlements with the National Health Fund for genetic tests in cancer under a contract of the hospital treatment type and under the contract in the type of separately contracted services between 2017 and 2019. RESULTS: The 150,647 diagnostic genetic tests were reported, which were billed to 111,872 patients. The average number of tests per patient was 1.35. One test was billed to 83.5% of patients, 11.2% of patients had two tests billed, and 5.3% had at least three tests billed. The number of services provided under the hospital treatment contract in 2018 doubled compared to the previous year. For separately contracted services, more than threefold increase in genetic testing performed in 2019 compared to 2018 was observed. CONCLUSION: our data show that the novel funding model for genetic services introduced in Poland has positive impact on the availability of genetic testing for patients.
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Neoplasias , Medicina de Precisão , Humanos , Oncologia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Testes Genéticos , PolôniaRESUMO
The delicate balance of funding research and development of treatments for rare disease is only imperfectly achieved in Europe, and even the current provisional equilibrium is under a new threat from well-intentioned policy changes now in prospect that could-in addition to the intrinsic complexities of research-reduce the incentives on which commercial activity in this area is dependent. The European Union review of its pharmaceutical legislation, for which proposals are scheduled to appear before the end of 2022, envisages adjusting the decade-old incentives to meet objectives that are more precisely targeted. However, researchers, physicians, patients and industry have expressed concerns that ill-considered modifications could have unintended consequences in disrupting the current balance and could reduce rather than increase the flow of innovative treatments for rare diseases.
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INTRODUCTION: In order to improve the efficacy of intravoxel incoherent motion (IVIM) parameters in characterising specific tissues, a new concept is introduced: the perfusion-diffusion ratio (PDR), which expresses the relationship between the signal S(b) decline rate as a result of IVIM and the rate of signal S(b) decline due to diffusion. The aim of this study was to investigate this novel approach in the differentiation of solid primary liver lesions. Material and Methods. Eighty-three patients referred for liver MRI between August 2017 and January 2020 with a suspected liver tumour were prospectively examined with the standard liver MRI protocol extended by DWI-IVIM sequence. Patients with no liver lesions, haemangiomas, or metastases were excluded. The final study population consisted of 34 patients with primary solid liver masses, 9 with FNH, 4 with regenerative nodules, 10 with HCC, and 11 with CCC. The PDR coefficient was introduced, defined as the ratio of the rate of signal S(b) decrease due to the IVIM effect to the rate of signal S(b) decrease due to the diffusion process, for b = 0. RESULTS: No significant differences were found between benign and malignant lesions in the case of IVIM parameters (f, D, or D ∗) and ADC. Significant differences were observed only for PDR, with lower values for malignant lesions (p = 0.03). The ROC analysis yielded an AUC value for PDR equal to 0.74, with a cut-off value of 5.06, sensitivity of 81%, specificity of 77%, and accuracy of 79%. CONCLUSION: PDR proved to be more effective than IVIM parameters and ADC in the differentiation of solid benign and malignant primary liver lesions.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Movimento (Física) , Perfusão , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Growing tumors avoid recognition and destruction by the immune system. During continuous stimulation of tumor-infiltrating lymphocytes (TILs) by tumors, TILs become functionally exhausted; thus, they become unable to kill tumor cells and to produce certain cytokines and lose their ability to proliferate. This collectively results in the immune escape of cancer cells. Here, we show that breast cancer cells expressing PD-L1 can accelerate exhaustion of persistently activated human effector CD4+ T cells, manifesting in high PD-1 and PD-L1 expression level son T cell surfaces, decreased glucose metabolism genes, strong downregulation of SWI/SNF chromatin remodeling complex subunits, and p21 cell cycle inhibitor upregulation. This results in inhibition of T cell proliferation and reduction of T cell numbers. The RNAseq analysis on exhausted CD4+ T cells indicated strong overexpression of IDO1 and genes encoding pro-inflammatory cytokines and chemokines. Some interleukins were also detected in media from CD4+ T cells co-cultured with cancer cells. The PD-L1 overexpression was also observed in CD4+ T cells after co-cultivation with other cell lines overexpressing PD-L1, which suggested the existence of a general mechanism of CD4+ T cell exhaustion induced by cancer cells. The ChIP analysis on the PD-L1 promoter region indicated that the BRM recruitment in control CD4+ T cells was replaced by BRG1 and EZH2 in CD4+ T cells strongly exhausted by cancer cells. These findings suggest that epi-drugs such as EZH2 inhibitors may be used as immunomodulators in cancer treatment.
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Rapid and continuing advances in biomarker testing are not being matched by uptake in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions-notably BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, the implementation of genetic testing in clinical routine setting is still challenging. Development is impeded by country-related heterogeneity, data deficiencies, and lack of policy alignment on standards, approval-and the role of real-world evidence in the process-and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework-starting with an update to outdated recommendations. We show herein the main issues and proposals that emerged during the previous advisory boards organised by the European Alliance for Personalized Medicine which mainly focus on possible scenarios of harmonisation of both oncogenetic testing and management of cancer patients.
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BACKGROUND: In Poland drug programmes developed by the Minister of Health and financed by the National Health Fund are special reimbursement frameworks of innovative, expensive, and mostly hospital based medical products used for a small number of patients. RESEARCH DESIGN: The research presented in this paper is based on data analysis published by the National Health Fund in Poland. The analysis focused on estimating public payer expenditure on drugs available within drug programmes from 2015 to 2018. RESULTS: In subsequent years, reimbursement of drugs used within drug programmes was associated with the National Health Fund budget expenditure of 635 mln USD, 755 mln USD, 854 mln USD, and 921 mln USD, respectively. Reimbursement of oncology drug programmes constituted 48.1%, 42.5%, 47.1%, and 52.4% and were approximately 305, 312, 402, 483 mln USD, whereas values of non-oncology drug programmes were approximately 330, 434, 452, and 438 mln USD which constituted 51.9%, 57.5%, 52.9%, and 47.6% respectively. CONCLUSION: Despite the fact that the expenditure on drug programs in Poland are increasing every year, they undoubtedly improve the patient's access to the most innovative oncological and nononcological therapies in the Polish healthcare system.
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Immunotherapy based on immune checkpoint inhibitors (ICIs) is currently broadly used in the treatment of different types of cancer. The treatment targeting programmed cell death protein 1/programmed death-ligand 1 axis is already approved by Food and Drug Administration for numerous cancers. These kinds of therapy brought spectacular results in the treatment of non-small cell lung cancer where systemic therapy was ineffective. However, a wide range of applied therapies based on ICIs in the clinic have led to unexpected side effects, such as severe cardiotoxicity. It needs to be underlined that the molecular mechanism of myocarditis in response to ICIs is still not fully understood. Lack of sufficient knowledge, especially concerning the kind of risk factors increasing probability of myocarditis, poses currently a large clinical problem. Continuous cardiac monitoring of patients who undergo ICI treatment presents another problem as it is cost-ineffective for the healthcare system. Herein, we highlight the risks of use of anticancer therapy based on ICIs. We also stress that detailed monitoring of any event of cardiotoxicity following ICIs treatment should be carefully investigated and registered to give a global overview of the frequency of myocarditis occurrence. Moreover, we propose that the extension of molecular and systemic knowledge of etiology of myocarditis as a side effect, including the role of protein kinases, will be highly beneficial for the medical field. Last but not least, better understanding of mechanisms of cardiotoxicity induction will improve the safety of cancer patients and will help clinicians in prediction of unexpected side effect occurrence.
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Cardiotoxicidade/etiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/terapia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Since developments are global in the healthcare arena, more should be done to align EU and other big markets' regulatory practices for rare disease patients. Notwithstanding efforts and cooperation between the US and EU aimed to harmonize their strategic plans in the field of orphan drugs, regulatory criteria and procedures to gain the designation, terms and classifications should be still harmonised. Aligning the criteria of prevalence and support to orphan medicines in the various jurisdictions internationally, would facilitate patient recruitment eventually at global level, so as to gain the data and the biological insights required to identify biomarkers and appropriate endpoints needed for progressing clinical development. A conducive regulatory environment can further support the development of medicines to treat rare diseases. Overall there is a need for joined-up regulatory process coordination. Better integration of regulatory pathways and better integration of regulatory systems, such as scientific tools and methods to generate evidence, would be helpful. There is a need to revise and agree the current frameworks to be improved which will take into account the considerations and challenges to diagnose and treat different rare diseases and improve quality of life. Deliberative processes with multi-stakeholders' involvement for reimbursement should be considered. This paper explores the successes and limitation of both the regulation and its implementation mechanisms in the current regulatory context, and suggests some improvements that could maximise its benefits and boost rare disease research even further.
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Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. This paper sets out the potential of biomarker testing, the unfolding precision and range of possible diagnosis and prediction, and the many obstacles to adoption. It offers case studies of biomarker testing in breast, ovarian, prostate, lung, thyroid and colon cancers, and derives specific lessons as to the potential and actual use of each of them. It also draws lessons about how to improve access and alignment, and to remedy the data deficiencies that impede development. And it suggests solutions to outstanding issues - notably including funding and the tangled web of obtaining reimbursement or equivalent coverage that Europe's fragmented health system implies. It urges a European evolution towards an initial minimum testing scenario, which would guarantee universal access to a suite of biomarker tests for the currently most common conditions, and, further into the future, to an optimum testing scenario in which a much wider range of biomarker tests would be introduced and become part of a more sophisticated health system articulated around personalised medicine. For exploiting genomics to the full, it argues the need for a new policy framework for Europe. Biomarker testing is not an issue that can be treated in isolation, since the purpose of testing is to improve health. Its use is therefore always closely linked to specific health challenges and needs to be viewed in the broader policy context in the EU and more widely. The paper is the result of extensive engagement with experts and decision makers to develop the framework, and consequently represents a wide consensus of views on how healthcare systems should respond from push and pull factors at local, national and cross-border and EU level. It contains strong views and clear recommendations springing from the convictions of patients, clinicians, academics, medicines authorities, HTA bodies, payers, the diagnostic, pharmaceutical and ICT industries, and national policy makers.
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PURPOSE: Adenoid cystic carcinoma (ACC) is a rare neurotropic cancer with slow progression occurring in salivary glands and less frequently in other body parts. ACC is featured by hyperchromatic nuclei and various mutations in genes encoding chromatin-related machineries. The ACC treatment is mainly limited to the radical surgery and radiotherapy while the chemotherapy remains ineffective. As the knowledge about molecular basis of ACC development is limited, we investigated here the molecular features of this disease. PATIENTS AND METHODS: This study included 50 patients with ACC. Transcript profiling of available ACC samples vs normal salivary gland tissue, quantitative real-time PCR (qRT-PCR) transcript level measurements and the immunohistochemistry (IHC) for SWI/SNF chromatin remodeling complex (CRC) subunits and androgen receptor on surgery-derived paraffin-embedded samples were performed. RESULTS: Transcriptomic study followed by Gene Ontology classification indicated alteration of chromatin-related processes, including downregulated transcript levels of main SWI/SNF CRC subunits and elevated expression of BRM ATPase-coding SMARCA2 gene in ACC. Subsequent IHC indicated broad accumulation of BRM ATPase and several SWI/SNF subunits, suggesting affected control of their protein level in ACC. The IHC revealed ectopic, heterogeneous expression of androgen receptor (AR) in some ACC cells. CONCLUSIONS: Our study indicated that ACC features aberrant expression of genes controlling chromatin status and structure. We found that the balance between SWI/SNF classes is moved towards the BRM ATPase-containing complex in ACC. As BRM is known to be involved in chemoresistance in cancer cells, this observation may be the likely explanation for ACC chemoresistance.
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Carcinoma Adenoide Cístico/patologia , Montagem e Desmontagem da Cromatina , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores Androgênicos/genética , Fatores de Transcrição/genética , Transcriptoma , Adulto JovemRESUMO
BACKGROUND: Primary Hepatic Epithelioid Haemangioendothelioma (HEHE) and Primary Hepatic Angiosarcoma (PHA) are rare mesenchymal tumours with different malignant potential. Whereas HEHE demonstrates low to intermediate malignant potential, PHA is an aggressive malignancy with poor prognosis. The knowledge of typical imaging features of these lesions may facilitate correct diagnosis; however, the ultimate diagnosis of HEHE and PHA is based on histopathologic examination. DISCUSSION: The most typical findings helpful in diagnosing HEHE are: Presence of multiple, confluent nodules located at the liver periphery (in young to middle-aged woman), retraction of the liver capsule, marked hyperintensity on T2-weighted images, "target-sign" appearance, progressive centripetal contrast enhancement, and relatively high Apparent Diffusion Coefficient (ADC) values. More than ≥50% of nodules are hyper- or isointense on Hepatobiliary Phase (HBP) images. CONCLUSION: The imaging features suggestive of PHA are: Occurrence of metastases (lungs, spleen) at the time of diagnosis, presence of a large dominant mass with smaller satellites, heterogeneity and areas of haemorrhage in a dominant mass, progressive contrast enhancement, slightly elevated ADC values as compared to other malignant liver tumours.
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Hemangioendotelioma , Hemangiossarcoma , Neoplasias Hepáticas , Imageamento por Ressonância Magnética/métodos , Meios de Contraste/administração & dosagem , Hemangioendotelioma/diagnóstico por imagem , Hemangioendotelioma/patologia , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologiaAssuntos
Centro Germinativo , Doença de Hodgkin , Linfadenopatia , Imageamento por Ressonância Magnética , Adulto , Idoso , Feminino , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/metabolismo , Humanos , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/metabolismo , Masculino , UltrassonografiaRESUMO
PURPOSE: To optimise the intravoxel incoherent motion (IVIM) imaging of the liver on a 3.0T scanner by assessing parameter reproducibility on free-breathing (FB) and respiratory-triggered (RT) sequences acquired with different numbers of signal averages (NSA). MATERIAL AND METHODS: In this prospective study 20 subjects (M/F: 10/10; age: 25-62 years, mean: 39 years) underwent IVIM magnetic resonance imaging (MRI) on a 3.0T scanner using an 18-channel phase-arrayed coil and four different echo-planar sequences, each with 10 b values: 0, 10, 30, 50, 75, 100, 150, 200, 500, and 900 s/mm2. Images were acquired with FB and RT with NSA = 1-4 (FBNSA1-4, RTNSA1-4) and with NSA = 3-6 (FBNSA3-6, RTNSA3-6). Subsequently, for the assessment of reproducibility of IVIM-derived parameters (f, D, D*), each subject was scanned again with an identical protocol during the same session. IVIM parameters were calculated. The distribution of IVIM-parameters for each DWI sequence were given as the median value with first and third quartile. Inter-scan reproducibility for each IVIM parameter was evaluated using coefficient of variance and Bland-Altman difference. Differences between FB sequence and RT sequence were tested using non-parametric Wilcoxon signed-rank test. RESULTS: Mean coefficient of variance (%) for f, D, and D* ranged from 60 to 64, from 58 to 84, and from 82 to 99 for FBNSA1-4 sequence; from 50 to 69, from 41 to 97, and from 80 to 82 for RTNSA1-4 sequence; from 22 to 27, 15, and from 70 to 80 for FBNSA3-6 sequence; and from 21 to 32, from 12 to, and from 50 to 80 for RTNSA3-6 sequence, respectively. CONCLUSIONS: Increasing the number of signal averages for IVIM acquisitions allows us to improve the reproducibility of IVIM-derived parameters. The sequence acquired during free-breathing with NSA = 3-6 was optimal in terms of reproducibility and acquisition time.
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INTRODUCTION: Cervical cancer is one of the most frequent malignant neoplasms in females. Such neoplasms can be almost completely eliminated by means of adequate primary and secondary prophylaxis. The most developed countries focus their attention on the improvement of prophylaxis systems, test quality, and efficacy improvement, as well as on the expansion of the primary prophylaxis. In Poland, the discussions focus on the improvement of the malfunctioning population programme. OBJECTIVE: Drawing on recent research findings, the article presents current Polish and global recommendations with regard to screening tests for cervical cancer. The results of the Population Programme of Prophylaxis and Early Detection of Cervical Cancer are discussed in the context of current trends of healthy behaviour among women inhabiting rural areas. DESCRIPTION OF THE STATE OF KNOWLEDGE: In the future, it will be relevant to increase the number of human papillary virus (HPV) tests as part of the prophylaxis programme, especially among the high risk patient group. In particular, there is a necessity to increase the number of vaccinations among young women, especially before the beginning of their sexual activity, as well as to establish new strategies of secondary prophylaxis in this group. At present, women who had been vaccinated should undergo routine screening. In Poland, the report based on SIMP registry (IT System of Prophylaxis Monitoring), shows that only 27% of the 3.3 million of invited women participated in the cytology tests. The data analysis shows that women living in rural areas more often respond and participate in the tests, compared to women living in the cities (39.3% vs. 16.8%).
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Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/fisiologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Polônia/epidemiologia , População Rural/estatística & dados numéricos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
We are, understandably, forever hearing about the high cost of bringing innovative new drugs and treatments to the healthcare market, especially medicines for smaller subgroups, and the fact that member state health systems often baulk at the prices. This article will argue that such a bypassing and blocking of innovative medicines and treatments is not only counterproductive when it comes to the health of Europe's patients, but actually fails to take into account the economic arguments. The article seeks to show that the long-term benefit to patients and the economy (health means wealth) will outweigh initial costs down the line. Couple this with a smarter use of information technologies and other resources and it will be possible to get much closer to building sustainable healthcare systems in a Europe struggling under the burden of an ageing population.
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AIM OF THE STUDY: was to analyze the outcome of treatment and factors predicting results of sorafenib therapy in inoperable/metastatic CD117-positive GIST patients after failure on imatinib and sunitinib. MATERIAL AND METHODS: We identified 60 consecutive patients (40 men, 20 women) with advanced inoperable/metastatic GIST after failure on at least imatinib and sunitinib treated in one sarcoma center with sorafenib at initial dose 2 × 400 mg daily in 2007-2015 (in 56 cases it was 3rd line therapy). Median follow-up time was 39 months. RESULTS: One year progression-free survival (PFS; calculated from the date of the start of sorafenib to disease progression) rate was 23% and median PFS = 7.7 months. The median overall survival (OS) was 13.5 months calculated from sorafenib start (1-year OS rate = 57%) and 7 years from imatinib start. Three patients (5%) had objective partial responses to therapy, 31 patients (52%) had stabilization of disease > 4 months. Primary tumor mutational status was known in 43 cases (73%), but we have not identified the differences in PFS between tumors carrying different KIT/PDGFRA mutations. The most common adverse events were: diarrhoea, hand and foot syndrome, fatigue, loss of weight and skin reactions; grade 3-5 toxicity occurred in 35% of patients. 23 patients required sorafenib dose reductions due to AEs. CONCLUSIONS: We confirmed that many advanced GIST patients benefit from sorafenib therapy after imatinib/sunitinib failure with OS > 1 year.
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BACKGROUND: Rhabdomyosarcoma is a solid tumor, resulting from dysregulation of the skeletal myogenesis program. For rhabdomyosarcomas (RMS) with a predilection for the head and neck, genitourinary tract, extremities, trunk, retroperitoneum, the larynx is still an unusual site. Till now only several cases of this laryngeal tumor have been described in world literature in the adult population. The entire spectrum of genetic factors underlying RMS development and progression is unclear until today. Multiple signaling pathways seem to be involved in ERMS development and progression. CASE PRESENTATION: In this paper we report an interesting RMS case in which the disease was located within the glottic region. We report an embryonal rhabdomyosarcoma of the larynx in 33 year-old man. After unsuccessful chemotherapy hemilaryngectomy was performed. In follow up CT no signs of recurrence were found. Recently patient is recurrence free for 62 months. CONCLUSIONS: Considering the histological diagnosis and the highly aggressive nature of the lesion for optimal diagnosis positron electron tomography (PET) and computerized tomography (CT) of the neck and thorax should be performed. At this time surgical treatment with adjuvant radiotherapy seems to be the treatment of choice for this disease. Rhabdomyosarcoma of the larynx has a better prognosis than elsewhere in the body, probably because of its earlier recognition and accessibility to radical surgery.
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Antineoplásicos/uso terapêutico , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/terapia , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/terapia , Adulto , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Traqueostomia , Resultado do TratamentoRESUMO
INTRODUCTION: Recently, concomitant radiochemotherapy became a method of choice in patients with poorly differentiated nasopharyngeal cancer. The aim of this study is to estimate tolerance and early results of the concomitant radiochemotherapy followed by adjuvant chemotherapy (modified US Head and Neck Intergroup protocol). METHODS AND MATERIAL: Analysing protocol consist of conventionally fractionated radiotherapy (TD = 70 Gy) given concomitantly with cisplatin (30 mg/m2 daily during 3 days every 3 weeks). This part of treatment was followed by 3 courses of PF (cisplatin + 5-fluorouracil) chemotherapy. Between August 1998 and September 2003 thirty six patients (27 male and 9 female) were qualified to treatment. Median age was 33 years. RESULTS: Tolerance of concomitant radiochemotherapy was acceptable. Intensive mucosal acute reactions (>G2) were observed in 67% patients. Life threatening complications (sepsis + DIC) was observed in single case. All patients received radiotherapy in planned total dose. Eighty six percent of patients received cisplatin in planned cumulated doses. Tolerance of the adjuvant chemotherapy was worse. Only 44% patients received all three courses of PF chemotherapy. The reasons of incomplete chemotherapy were neutropenia, infections, prolongated acute reactions or performance status decreasing. Complete regression was obtained in 86% patients. Two years overall and disease free survival rates were 83% and 72%, respectively. CONCLUSIONS: Our results confirm high activity of the concomitant radiochemotherapy followed by chemotherapy in patients with poorly differentiated nasopharyngeal cancer. Those results confirm also high toxicity of this regimen, what suggest very careful patients qualification to treatment.